Yttrium-90 Ibritumomab Tiuxetan Followed by Rituximab Maintenance as Treatment for Patients with Diffuse Large B-Cell Lymphoma Are Not Candidates for Autologous Stem Cell Transplant

2015 ◽  
Vol 133 (4) ◽  
pp. 347-353 ◽  
Author(s):  
Jon E. Arnason ◽  
Katarina Luptakova ◽  
Jacalyn Rosenblatt ◽  
Dimitrios Tzachanis ◽  
David Avigan ◽  
...  

Background: Not all patients with diffuse large B-cell lymphoma (DLBCL) are candidates for aggressive regimens. 90Y ibritumomab tiuxetan (90Y-IT), an anti-CD20 radionuclide-conjugated antibody, has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile. Methods: This phase II trial investigated the overall response rate (ORR), event-free survival (EFS), overall survival (OS) and toxicity of treatment with 90Y-IT (0.4 or 0.3 mCi 90Y/kg based on platelets) followed by rituximab maintenance therapy in patients with DLBCL not candidates for transplant. Results: 25 patients were enrolled. At best response 8 patients obtained a complete response (CR) and 1 a partial response (ORR 36%). Median EFS was 2.5 months and OS 8.1 months. No patient who obtained CR later relapsed systemically. Two patients were free of disease at the 61- and 100-month follow-ups; 65% had grade 3/4 thrombocytopenia, but no significant bleeding was observed. Grade 3 nonhematologic toxicity occurred in 36%. Patients who had progressed through a rituximab-containing regimen responded poorly. Conclusion: The ORR of 36% with 90Y-IT as salvage therapy for DLBCL while inferior to more aggressive regimens is significant with acceptable toxicity. For a subset of patients not candidates for salvage with autologous transplant, this treatment strategy can produce a durable, long-lasting remission.

2019 ◽  
Vol 3 (14) ◽  
pp. 2230-2236 ◽  
Author(s):  
Michael R. Bishop ◽  
Richard T. Maziarz ◽  
Edmund K. Waller ◽  
Ulrich Jäger ◽  
Jason R. Westin ◽  
...  

Abstract Tisagenlecleucel demonstrated high rates of durable responses in adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. Most patients (92%) received bridging therapies to control disease after study entry and before tisagenlecleucel infusion. Here, we examine the efficacy and safety of tisagenlecleucel in the subset of 7 patients who achieved complete response (CR) after bridging therapy and before tisagenlecleucel infusion. Tisagenlecleucel rapidly expanded in all 7 patients, and the transgene levels were measurable for up to 2 years after infusion. After infusion, all 7 patients were still in CR at the month 3 evaluation, and 5 of 7 patients remained progression-free >12 months. Adverse events were similar to the overall JULIET population. Cytokine release syndrome (CRS) was reported in 4 of 7 patients (grade 2 = 2 and grade 3 = 2 using the Penn grading scale), and 1 patient experienced grade 1 neurotoxicity. No patient required tocilizumab or steroids for CRS management. These data provide preliminary evidence of tisagenlecleucel efficacy in patients with r/r DLBCL without detectable disease after bridging or salvage therapies and warrant further investigation of tisagenlecleucel as consolidative therapy in future trials. This trial was registered at www.clinicaltrials.gov as #NCT02445248.


Author(s):  
Michael Northend ◽  
William Wilson ◽  
Wendy Osborne ◽  
Christopher P. Fox ◽  
Andrew John Davies ◽  
...  

The addition of polatuzumab vedotin to bendamustine and rituximab (Pola-BR) has been shown to improve overall survival (OS) in stem cell transplant (SCT)-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). It is also increasingly used as bridging to CAR T-cell therapy (CAR-T). We retrospectively analysed the efficacy of Pola-BR in 133 patients at 28 UK institutions. Treatment intent was bridging to CAR-T for N=40, re-induction with planned SCT for N=13 and stand-alone treatment for N=78. The overall response rate (ORR) was 57.0% (complete response (CR) 32.8%). After median 7.7 months follow-up, median PFS and OS were 4.8 months and 8.2 months respectively. For stand-alone treatment shortened PFS was associated with bulk disease (>7.5cm) (HR 2.32 (95% CI 1.23-4.38), p=0.009), >1 prior treatment (HR 2.17 (95% CI 1.19-3.95), p=0.01) and refractoriness to the last treatment (HR 3.48 (95% CI 1.79-6.76), p<0.001). For CAR-T bridging the ORR was 42.1% (CR 18.4%) and for treatment after CAR-T failure the ORR was 43.8% (CR 18.8%). These data demonstrate efficacy for Pola-BR as a treatment for SCT-ineligible patients with R/R DLBCL, help to delineate which patients may benefit most, and provide preliminary evidence of efficacy as bridging to CAR-T and after CAR-T failure.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2707-2707
Author(s):  
Pieternella J Lugtenburg ◽  
Josée M Zijlstra ◽  
Jeanette K Doorduijn ◽  
Lara H Böhmer ◽  
Marinus van Marwijk Kooy ◽  
...  

Abstract Background: Patients with relapsed/ refractory diffuse large B-cell lymphoma (DLBCL) after- or not eligible for autologous stem cell transplantation (ASCT) have a poor prognosis. Treatment with salvage chemotherapy has generally been disappointing. In many centers in the Netherlands the oral PECC regimen is used for such patients. 90Y-ibritumomab tiuxetan (Zevalin®, Spectrum Pharmaceuticals) radioimmunotherapy (RIT) is clinically active as a single agent in relapsed DLBCL. We conducted a prospective multi-center phase II study evaluating salvage therapy with Rituximab (R)-PECC, in responsive patients followed by 90Y-ibritumomab tiuxetan consolidation. Methods: Adult patients with refractory/relapsed DLBCL, more than one year after or not eligible for ASCT, were treated with R-PECC (Prednisone 40 mg/m2 po D1-5; Etoposide 100 mg/m2 po D1-5; Chlorambucil 8 mg/m2 po D1-5; Lomustine 80 mg/m2 po D1 and Rituximab 375 mg/m2 iv D1) q 28 days for 4 cycles. Complete (CR) or partial responders (PR) received consolidation with a single dose 90Y-ibritumomab tiuxetan (15 MBq/kg, 0.4 mCi/kg). Response was evaluated according to the revised Cheson criteria (2007). Results: Between November 2008 and February 2012 62 patients were enrolled. Median age was 70 years (range, 45-82). Secondary IPI score was high-intermediate or high in 42% patients. All patients had received CHOP at first-line, 12 without rituximab. Prior therapies consisted of (R)-CHOP (65%), R-CHOP and R-DHAP/VIM (24%) or R-CHOP and R-DHAP/VIM plus ASCT (11%). Fourteen patients (23%) were refractory to the last prior therapy. After 4 cycles of R-PECC the overall response rate (ORR) was 31/62 (50%), with 14 of 62 (23%) patients achieving a CR and 17 of 62 (27%) achieving a PR, 13 of 62 (21%) patients had progressive disease. ORR of relapsed patients was significantly higher than that of patients refractory to their last prior treatment (63% vs 7%, p=0.0001). 29 of 31 responsive patients received consolidation with RIT. The remaining two patients with PR did not proceed to RIT because of one toxic death and one misinterpretation of the response. The ORR after the end of the entire treatment was 29% (23% CR, 6% PR), RIT consolidation improved the overall best response (from PR to CR) in 5 of the 17 PR pts after the R-PECC only regimen. The median follow-up time of patients still alive is 48 months (range, 0-67 months). The median response duration in the patients that received R-PECC only was 9 months (range 3-63 months). The median response duration in the patients that received RIT consolidation was 20 months (range 0-59 months). The failure free survival at 1 yr from start of RIT consolidation was 52% (95% CI=[33%,68%]) and the overall survival 62% (95% CI=[42%,77%]). There was one treatment related death, due to sepsis and pneumonia after the first R-PECC cycle. The R-PECC regimen was well tolerated by most patients. The most common grade 3 or 4 adverse events during R-PECC treatment were hematological toxicity (27%), infection (19%) and malaise (11%). Adverse events after RIT were primarily hematologic. Grade 3 to 4 trombocytopenia and neutropenia occurred in 8 patients (28%) and 5 patients (17%), respectively. Eight patients received platelet transfusions and 6 patients red blood cell transfusions. Conclusions: The R-PECC regimen shows good clinical activity in relapsed DLBCL patients. Its activity in refractory patients is low. This largely oral regimen provides patients not eligible for high-dose salvage treatment with a convenient treatment schedule with an acceptable safety profile. Consolidation with RIT was well tolerated and resulted in long response durations in half of the patients. Disclosures Lugtenburg: Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Roche: Consultancy; Celgene: Consultancy. Off Label Use: 90Ytrium-ibritumomab tiuxetan for diffuse large B-cell lymphoma. Zijlstra:Celgene: Consultancy; Roche: Consultancy. Doorduijn:Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Hoogendoorn:Gilead: Consultancy; Novartis: Consultancy.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8558-8558
Author(s):  
Jon E. Arnason ◽  
Katarina Luptakova ◽  
Jacalyn Rosenblatt ◽  
Jeffrey Zwicker ◽  
James D. Levine ◽  
...  

8558 Background: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) are salvaged with high dose chemotherapy followed by autologous stem cell rescue. Ibritumomab tiuxetan is an anti-CD20 antibody conjugated to the radionuclide 90yttrium. 90Y ibritumomab tiuxetan has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile relative to transplant. Methods: This phase II trial investigated the overall response rate (ORR), event free survival (EFS), overall survival (OS) and toxicity of treatment with ibritumomab followed by rituximab in patients with relapsed or refractory DLBCL, not candidates for transplant. Patients were treated with an initial dose of rituximab (250 mg/m2) followed one week later by ibritumomab (0.4 mCi90Y/kg or 0.3 mCi90Y/kg based on plateles) followed by 4 weekly doses of rituximab (375mg/m2). All non-progressing patients received maintenance rituximab (375 mg/m2) weekly for 4 doses every 6 months for 4 cycles. Results: 25 patients were enrolled. Median age was 79 (range 45-95). 12 of 25 (48%) had stage 3 or 4 disease. 13 (52%) had 2 or more prior regimens. At 12 weeks 5 patients (21%) had a complete response (CR), 3 (13%) a partial response, 2 (8%) stable disease and 14 (58%) progressed for an ORR of 32% (8/25). At best response 7 patients obtained a CR. Median EFS was 2.5 months. Median OS was 8.1 months. No patient who obtained CR later relapsed, with follow up of 18.3-100.1 months. Deaths unrelated to treatment occurred in remission in 5 patients. 2 patients remain free of disease at 67.4 and 100.1 months. 11 (65%) patients had grade 3 or 4 thrombocytopenia, but no significant bleeding was observed. 9 (36%) patients had grade 3 non-hematologic toxicity. Grade 1 and 2 fatigue occurred in 41%. Patients who progressed through a rituximab containing regimen were at high risk of early progression. Conclusions: The ORR of ibritumomab as salvage therapy for DLBCL compares favorably to other regimens with acceptable toxicity. Those patients with disease refractory to rituximab are not likely to benefit. For a subset of patients not candidates for salvage with autologous transplant, this treatment can produce a durable remission. Clinical trial information: NCT00110149.


Author(s):  
Walid Shalata ◽  
Ismaell Massalha ◽  
Kayed Al-Athamen

In this report, we describe a 38-year-old male with a very rare type of lymphoma, large B cell lymphoma with T cell-rich background and nodules lacking follicular dendritic cell meshworks (THRLBCL). In 2016 the patient presented hot flashes and night sweats (B-symptoms) and peripheral edema. He was treated with R-CHOP (doxorubicin, vincristine, cyclophosphamide, rituximab and Prednisone) chemotherapy, a Positron emission tomography–computed tomography (PET-CT) scan was performed after four cycles of treatment which showed radiologic complete response and blood test (complete blood count (CBC)) results showed normal ranges. As of September, 2020 he patient remains in complete remission. We searched the literature for descriptions of cases spanning the diagnostic spectrum of THRLBCL and we identified only five cases worldwide. The last reported case was in 2014 with distinctive features that were difficult to classify according to the World Health Organization criteria or previously described variants. Our patient is the sixth case of THRLBCL to be reported. He is the youngest of the reported cases and the first from Israel and the Middle East.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mu-Chen Zhang ◽  
Ying Fang ◽  
Li Wang ◽  
Shu Cheng ◽  
Di Fu ◽  
...  

Abstract Background Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). Results Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. Conclusion CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.


2018 ◽  
Vol 18 ◽  
pp. S294 ◽  
Author(s):  
Arnav Sethi ◽  
G. Obi ◽  
A. Manhas ◽  
A. Scholoff ◽  
N. Vu ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2770-2770
Author(s):  
Luis Fayad ◽  
Michael Overman ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Felipe Samaniego ◽  
...  

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4441-4441
Author(s):  
Makoto Kodaira ◽  
Masahiro Yokoyama ◽  
Hiroaki Asai ◽  
Shuhei Yamada ◽  
Kyoko Ueda ◽  
...  

Abstract <Background> Patients with relapsed and refractory diffuse large B-cell lymphoma are usually treated with platinum-based salvage chemotherapy. We retrospectively analyzed the efficacy of adding rituximab with ICE as a salvage treatment for relapsed and refractory diffuse large B-cell lymphoma. <Method>From November 2003 to December 2006, patients with relapsed or refractory de novo diffuse large B-cell lymphoma represented CD20 positivty who received R-ICE (rituximab375mg/m2, Ifosfamide 1200mg/m2, calboplatin 400mg/m2 and etopside100mg/m2 ), were analyzed retrospectively. <Result>23 patients (19 relapse and 4 reflactory) (M:F=14:9) (median age 69, 28–77) were included. At starting treatment, twelve patients received rituximab and 11 patients were rituximab naive. In all 23 patients, responses were 11 Complete remission (CR), and 6 partial response (PR), resulting in overall response (ORR) was 74.9%. With median follow up of 10.5 months, estimated 1yr-progression free survival (PFS) was 49% and 1yr-overall survival (OS) was 70%.In patients received rituximab, ORR was 66.7% and 5 patiets achieved CR (41.7%).In the without rituximab, ORR was 90.9% and 7 patiets achieved CR (63.6%). No statistical differences were observed in response even with retuximab pretreatment. Estimated 1yr-PFS was 23% and 70% (p=0.0752) and 1yr-OS was 59% and83% (P=0.0049),respectively. NCI-CTC grade 3/4 neutropenia and thrombocytopenia were reported 100% and 91%, For non-hematological adverse event, there were grade 3 liver dysfunction (2/23) and grade 3 arrythmia (1/23). No toxic death was reported in this study. <Conclusion> R-ICE showed promising efficacy with tolelable toxicity. Available date suggested adding rituximab to ICE is more effective for patients not received rituximab in the pretreament.


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